Biomaterial Database

Sleep-wake characterization of double MT₁/MT₂ receptor knockout mice and comparison with MT₁ and MT₂ receptor knockout mice. 2013

Stefano Comai, and Rafael Ochoa-Sanchez, and Gabriella Gobbi

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada.

The neurohormone melatonin activates two G-protein coupled receptors, MT1 and MT2. Melatonin is implicated in circadian rhythms and sleep regulation, but the role of its receptors remains to be defined. We have therefore characterized the spontaneous vigilance states in wild-type (WT) mice and in three different types of transgenic mice: mice with genetic inactivation of MT1 (MT1(-/-)), MT2 (MT2(-/-)) and both MT1/MT2 (MT1(-/-)/MT2(-/-)) receptors. Electroencephalographic (EEG) and electromyographic sleep-wake patterns were recorded across the 24-h light-dark cycle. MT1(-/-)mice displayed a decrease (-37.3%) of the 24-h rapid eye movement sleep (REMS) time whereas MT2(-/-)mice showed a decrease (-17.3%) of the 24-h non rapid eye movement sleep (NREMS) time and an increase in wakefulness time (14.8%). These differences were the result of changes occurring in particular during the light/inactive phase. Surprisingly, MT1(-/-)/MT2(-/-) mice showed only an increase (8.9%) of the time spent awake during the 24-h. These changes were correlated to a decrease of the REMS EEG theta power in MT1(-/-)mice, of the NREMS EEG delta power in MT2(-/-)mice, and an increase of the REMS and wakefulness EEG theta power in MT1(-/-)/MT2(-/-) mice. Our results show that the genetic inactivation of both MT1 and MT2 receptors produces an increase of wakefulness, likely as a result of reduced NREMS due to the lack of MT2 receptors, and reduced REMS induced by the lack of MT1 receptors. Therefore, each melatonin receptor subtype differently regulates the vigilance states: MT2 receptors mainly NREMS, whereas MT1 receptors REMS.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008809	Mice, Inbred C3H	An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research.	Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003700	Delta Rhythm	Brain waves seen on EEG characterized by a high amplitude and a frequency of 4 Hz and below. They are considered the "deep sleep waves" observed during sleep in dreamless states, infancy, and in some brain disorders.	Delta Rhythms,Rhythm, Delta,Rhythms, Delta
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012894	Sleep Stages	Periods of sleep manifested by changes in EEG activity and certain behavioral correlates; they formerly included Stage 1: sleep onset, drowsy sleep; Stage 2: light sleep; Stages 3 and 4: delta sleep, light sleep, deep sleep, telencephalic sleep. In 2007, sleep stages were redefined by The American Academy of Sleep Medicine (AASM) as: N1-N2 (sleep onset - light sleep), N3 (SLOW-WAVE SLEEP), and REM SLEEP.	N1-Sleep,N2-Sleep,NREM Stage 1,NREM Stage 2,N1 Sleep,N2 Sleep,Sleep Stage,Stage, Sleep,Stages, Sleep
D012895	Sleep, REM	A stage of sleep characterized by rapid movements of the eye and low voltage fast pattern EEG. It is usually associated with dreaming.	Fast-Wave Sleep,Paradoxical Sleep,Rapid Eye Movements,Rhombencephalic Sleep,Sleep, Fast-Wave,REM Sleep,Eye Movement, Rapid,Eye Movements, Rapid,Fast Wave Sleep,Movement, Rapid Eye,Movements, Rapid Eye,Rapid Eye Movement,Sleep, Fast Wave,Sleep, Paradoxical,Sleep, Rhombencephalic
D013826	Theta Rhythm	Brain waves characterized by a frequency of 4-7 Hz, usually observed in the temporal lobes when the individual is awake, but relaxed and sleepy.	Rhythm, Theta,Rhythms, Theta,Theta Rhythms
D014851	Wakefulness	A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli.	Wakefulnesses